Epigenetics in vascular disease - therapeutic potential of new agents.
2014
Vascular diseases, including atherosclerosis, angioplasty-induced restenosis, vessel graft arteriosclerosis and
hypertension-related stenosis, remain the most prevalent cause of death in the developed world. The aetiology of vascular
diseases is multifactorial with both genetic and environmental factors. Recently, some of the most promising research
identifies the epigenetic modification of the genome to play a major role in the disease development, linking the environmental
insults with gene regulation. In this process, modification of DNA by methylation, and histone modification by
acetylation, methylation, phosphorylation and/or SUMOylation are reported. Importantly, recent studies demonstrated that
histone deacetylase (HDAC) enzymes are crucial in endothelial integrity, smooth muscle proliferation and in the formation
of arteriosclerosis in animal models. The study of HDACs has shown remarkable specificity of HDAC family members
in vascular cell growth/death that influences the disease process. Interestingly, the effects of HDACs on arteriosclerosis
development in animal models have been observed after HDAC inhibition using specific inhibitors. This provides a
new approach for the treatment of vascular disease using the agents that influence the epigenetic process in vascular cells.
This review updates the rapid advances in epigenetics of vascular diseases focusing on the role of HDAC family in atherosclerosis.
It will also discuss the underlying mechanisms of histone acetylation in vascular cells and highlight the therapeutic
potential of such agents.
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